Nasal epinephrine spray outcomes comparable with autoinjector, manual injections
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Key takeaways:
- Intranasal spray had faster and higher maximum concentrations than autoinjectors and manual syringes.
- The spray and autoinjector delivery had similar effects on blood pressure and heart rate.
An intranasal epinephrine spray produced pharmacokinetic and pharmacodynamic results that were comparable or superior to intramuscular injections, according to a study published in The Journal of Allergy and Clinical Immunology: Global.
This spray may be a viable alternative to intramuscular epinephrine autoinjectors (EAIs) for patients who are afraid of needles, improving carriage and administration rates, researchers wrote.
Challenges with injections
“Patients often do not regularly carry their EAI on their person, so they may not have access to an EAI when needed in an emergency,” Karen Rance, DNP, CPNP, vice president and head of medical affairs at Bryn Pharma, told Healio. “EAIs are large and bulky and contribute to the documented reason for low carriage.”
Rance, who was not one of the authors of the study but is employed by the spray’s manufacturer, noted that 22% of patients at risk for anaphylaxis do not carry their EIAs regularly and that 37% do not carry them because they are too big and bulky.
EAIs present other disadvantages as well, Rance continued. For example, the needle length of an EAI may be too short for patients with obesity or too long for young children and infants with smaller skin-to-bone distances.
Also, she said, the recommended maximum dose for an EAI, which is 0.5 mg, is unavailable in the United States.
“Studies have demonstrated that an inadequate initial dose of epinephrine may increase the risk for a biphasic anaphylactic reaction,” Rance said.
Patient hesitation in using EAIs is well documented as well, she continued, largely due to the uncertainty or fear of not using the device correctly.
“Patients and caregivers may also underuse devices due to lack of training, embarrassment or needle phobia,” Rance said, adding that needle phobia is real.
In fact, Rance said, the percentage of children with needle phobia increased from 25% in 1995 to 65% in 2012 for those children born after 1999, possibly because of increases in booster shots administered around age 5 years.
“This is when children are old enough to remember the experience but young enough to be more susceptible to developing a phobia,” she said.
Approximately 10% to 25% of adults experience an intense fear of needles or injections, Rance added.
“It is likely that the actual number is more significant because the most severe cases are never documented due to the tendency of the sufferer to avoid all medical treatment,” she said.
Incorrect EAI use can lead to injury too, Rance said, adding that it is essential to follow proper administration techniques to minimize the risk for injury.
Study design, results
NDS1C (Bryn Pharmaceutics) is a nasal spray that administers epinephrine without the need for a needle. It is designed to be small enough to fit in a pocket, and it can be used without any specialized medical training, Rance said.
“The purpose of developing NDS1C is to offer an epinephrine product for the allergy community that is similar to the EpiPen (Viatris/Myan Specialty) autoinjector, which is the preferred treatment for outpatients,” she said.
The study included 101 healthy adults in a pair of cohorts. Participants received two consecutive 6.6 mg doses of NDS1C totaling 13.2 mg, administered within 10 seconds of each other; a 0.3 mg intramuscular epinephrine injection (USP Autoinjector); and a 0.5 mg intramuscular injection with a manual syringe, with each of these administered approximately a day apart. Cohort 1 (n = 51) received one dose of the nasal spray in each nostril, and cohort 2 (n = 50) received their doses in the same nostril.
Researchers conducted pharmacokinetic sampling before each dose and 6 hours after each dose.
The highest epinephrine exposures occurred after the opposite-nostril doses of the nasal spray, followed by the same-nostril doses, the manual syringe doses, and then the autoinjector doses. Intranasal administration also produced a single peak that was greater than the peaks that followed intramuscular administration, the researchers found.
Intranasal treatment in cohorts 1 and 2 produced higher areas under the curve (AUC; AUC through 360 minutes, 39,060 pg*min/mL vs. 17,440 pg*mL) and maximum concentrations (Cmax; 429.4 pg/mL vs. 328.6 pg/mL), in addition to similar AUC results for 0 to 10 minutes (AUC0-10), compared with autoinjector administration. Similar results were seen compared with the manual syringe, although AUC results for time to maximum concentration were lower with intranasal treatment. Specifically, times to maximum concentration included 20 minutes for NDS1C, 14.9 minutes for the autoinjector and 45 minutes for the manual syringe.
Also, 27 of 54 participants who received opposite-nostril administration achieved the same epinephrine levels produced by the autoinjector with a median time of approximately 8.2 minutes, with the same seen in 33 of the 49 participants with same-nostril administration after 6.2 minutes.
AUC and Cmax results for opposite-nostril administration were approximately 9% to 30% higher than same-nostril administration.
Pharmacodynamic results for nasal, autoinjector and manual syringe administration were similar as well, the researchers found, with no significant deviations.
In cohort 1, opposite-nostril treatment had slightly higher mean changes from baseline in heart rate values than autoinjector and manual syringe administration through 60 minutes after the dose, with no other remarkable differences, the researchers wrote.
Cohort 2 did not have any remarkable differences between the modes of administration in mean changes from baseline heart rate.
There were minimal and comparable changes in systolic blood pressure across treatments in cohort 1, although opposite-nostril administration had slightly greater decreases from baseline between 20 and 180 minutes after dosing compared with autoinjector and manual syringe administration. Changes in baseline systolic blood pressure values in cohort 2 were minimal and comparable across all modes of administration.
There were no deaths or serious adverse events in either cohort, with 49 (74%) of participants in cohort 1 reporting 219 adverse events and 33 (66%) participants in cohort 2 reporting 105 adverse events. The researchers said that most of these events were commonly associated with administration of epinephrine.
Conclusions, next steps
Based on these findings, the researchers said that intranasal epinephrine has an enhanced pharmacokinetic profile compared with autoinjector administration. Also, the researchers suggested that intranasal epinephrine may decrease delays in administration that have been observed with autoinjector delivery and improve patient carry rates as well, optimizing clinical outcomes.
In February 2019, the FDA granted Bryn Pharma’s developmental program a fast track designation. The company now is pursuing a new drug application pathway by comparing NDS1C in a pivotal clinical trial against the reference listed drug, the 0.3 mg intramuscular autoinjector.
“We are working to complete our clinical development program and look forward to working with the FDA to bring a needle-free option to the market as soon as possible,” Rance said. “We are confident that, if approved, NDS1C will offer a novel, practical and convenient alternative to needle-based administration routes to help overcome some of the persisting barriers that cause patients and caregivers experiencing an anaphylactic attack to delay or avoid treatment.”